Nanofabrication achieved on a biological substrate

HANCOCK, N.H.  Dip-pen nanolithography, a process being developed for ultrasmall feature definition on semiconductor ICs, may blaze new trails in medicine as well, if preliminary work reported at the fall meeting of the Materials Research Society can be turned into practical procedures.

Albena Ivanisevic, a bioengineer at Purdue University's Bindley Bioscience Center (West Lafayette, Ind.), described a process in which amino acid-based nanostructures were assembled on retinal tissue. The structures might be useful to surgeons trying to correct blindness caused by macular degeneration.

The technical feat highlights the versatility of dip-pen nanolithography, which can build features at 10-nanometer dimensions on virtually any substrate.

"We wanted to demonstrate that we could perform lithography, or patterning, on something other than a metal, semiconductor or insulator surface," Ivanisevic said.

Working with Nicole Onyenenho from the University of Maryland, Ivanisevic built templates from peptides to support transplanted cells that are critical for nourishing light-sensitive cells in the retina. Macular degeneration occurs because the natural cells performing that function degenerate, leading to the death of light-sensitive neurons and the onset of blindness.

The dip-pen approach is a modification of atomic-force microscope (AFM) technology and is promising for building biomimetic templates for a wide variety of biological applications, Ivanisevic said. A specific pattern to be constructed is first programmed into the control computer that guides the tip. The tip is dipped in a solution containing the molecules that are to be deposited. When scanned across a substrate, a tiny droplet of water attached to the tip allows the molecules to slide off.

The process was invented by Chad Mirkin at Northwestern University, who later founded NanoInk Inc. (Chicago) with the aim of commercializing it. In the procedure Ivanisevic described, the retinal tissue was first extracted from a pig's eye.

The dip-pen process can be controlled by a number of parameters to create complex structures on a surface, Ivanisevic explained. Adhesion forces change with topography and the biomolecules at the tip and on the substrate provide added control over the end result. The dip-pen system can provide instantaneous feedback on the molecular forces involved, allowing bioengineers quite a bit of design freedom in creating simple or complex structures, she said.

Tests showed that the templates created from the peptides were firmly attached to the retinal tissue. The researchers are trying out a number of different biomimetic templates to see which configurations are best for allowing the growth of retinal-pigment epithelial cells, which are the cells that sustain the light-sensitive neurons in the retina.

Mirkin also appeared at the conference to detail recent advancements for his nanolithography technique. The basic pen action depends on surface tension, which draws molecules off the tip of an AFM cantilever and deposits them on a substrate. More control over that basic physical force is being introduced via electromagnetic fields. A process described as "electronic whittling" uses electrical pulses to stimulate deposition at edge sites on the substrate. Features that would be around 300 nm were reduced to 150 nm using the electromagnetically enhanced technique.

Mirkin expects the new technique will be used to create DNA and protein arrays on biochips and may also assist in the creation of molecular electronic systems.